Trans-4-aminomethyl cyclohexane-1-carboxylic acid (hereinafter referred to as trans-AMCHA) has an antiplasmic activity and, therefore, is medicinally useful as an antiplasmic agent. For the production of trans-AMCHA, there have heretofore been proposed various methods such as (1) through (3) below.
1. A method for converting cis-4-aminomethyl cyclohexane-1-carboxylic acid (hereinafter referred to as cis-AMCHA) into trans-AMCHA by heating cis-AMCHA or a mixture of cis-AMCHA with trans-AMCHA (hereinafter referred to as cis-trans-AMCHA mixture) in water as the solvent in the presence of an alkali hydroxide, alkali carbonate or alkali hydrogen carbonate at temperatures in the range of from 160.degree. C to 250.degree. C under pressure (Japanese Patent Publication No. 14830/1966). PA1 2. A method for converting cis-AMCHA into trans-AMCHA by heating cis-AMCHA or cis-trans-AMCHA mixture in water as the solvent in the presence of the hydroxide or oxide of an alkaline earth metal under pressure (Japanese Patent Publication No. 23018/1967). PA1 3. A method for converting cis-AMCHA into trans-AMCHA by heating cis-AMCHA or cis-trans-AMCHA mixture in the presence of hydrochloric acid or sulfuric acid (Japanese Patent Publication No. 27506/1972). PA1 4. A method which includes converting the trans component and the cis component of the trans-cis-AMCHA into respective paratoluene sulfonates and separating the trans component in the form of sulfonate by virtue of the difference in solubilities of the two paratoluene sulfonates (Japanese Patent Publications No. 28810/1968 and No. 16974/1968). PA1 5. A method for isolatng trans-AMCHA in the form of a sulfate, iodate or sulfosalicylate (Japanese Patent Publication No. 27506/1972). PA1 6. A method for isolating trans-AMCHA in the form of a phthalic acid or phthalate (Japanese Patent Publication No. 24893/1967). PA1 7. A method for isolating trans-AMCHA in the form of a copper salt (Japanese Patent Publication No. 4784/1966).
In the conventional techniques described above, however, the trans-AMCHA products obtained thereby do not have high purity and are in the form of a mixture containing a fairly large proportion of cis-AMCHA (hereinafter this mixture will be referred to as trans-cis-AMCHA). In order to obtain trans-AMCHA of high purity suitable for medicinal use, it is necessary to separate trans-AMCHA from the trans-cis-AMCHA such as by one of the following methods (4) through (7) below.
In the production of trans-AMCHA of high purity, the conventional techniques have inevitably necessitated combination of an isomerization step for converting cis-AMCHA into trans-AMCHA and a separation step for isolating trans-AMCHA from the resultant trans-cis-AMCHA as described above. The techniques thus have the disadvantage that the operations involved are both time-consuming and complicated. In the production of trans-AMCHA of high purity, the conventional techniques also require an isomerization reaction to proceed in water as the solvent in the presence of an acid or alkali. Since this isomerization reaction is accompanied by secondary reactions as hydrolysis and polymerization, it is difficult for the conventional techniques to afford trans-AMCHA in high yields. Moreover, since the reaction vessels used for the isomerization reaction contain aqueous solutions of acids of alkalis at elevated temperatures under pressure, corrosion represents a serious problem. The conventional techniques, therefore, require for use in the isomerization process quite expensive vessels capable of withstanding the corroding action of the aqueous solutions.